Grant Award 008

Project Summary: The long-term benefit of this proposal is to develop a treatment for LBM2. The treatment is based on the autologous transplantation to the patients of their own myoblasts genetically corrected in vitro, i.e. introduction of the normal GNE gene with a viral vector. My research group became interested in the Hereditary Inclusion Body Myopathy (HTBM) following several e-mail messages from Dr. Daniel Darvish inquiring about our myoblast transplantation results. We have already cloned the GNE-cDNA by RT-PCR. Since there is no antibody available for the GNE protein, we have attached a code for a epitope tag (called V5) for which there is a commercially available antibody. This will permit us to do some preliminary experiments while developing polyclonal and monoclonal antibody. We have recently made a retroviral vector containing the GNE-V5 gene. We would now like to test this retroviral vector on human cells human patient myoblasts. We have thus recently obtained the permission from the human ethic committee the permission to obtain muscle biopsies from IBM2 patients. The genetically modified IBM2 myoblasts will be transplanted to SCID mice to verify the presence of muscle fibers expressing the transgene (GNE-V51). Although this initial grant proposal does not include the re-transplantation of the genetically corrected myoblasts to the patients, this grant will permit to develop all the tools (i.e., viral vectors and antibodies) required to start such a clinical trial subsequently.